Friedreich ataxia (FRDA) is associated with reduction of expression of and/or mutation in the FXN gene that encodes for the mitochondria protein frataxin. FRDA is an autosomal recessive disease, meaning individuals only develop this disease if they inherit a defective gene from both parents. FRDA is caused by mutations in the FXN gene that results in reduction of mRNA and protein levels of frataxin. Defective frataxin expression causes critical metabolic changes, including redox imbalance and ATP deficiency.
FRDA is a neurodegenerative disease that affects children and young adults and leads to progressive disability and premature death. Neurological signs are associated with degeneration of sensory neurons and the flow of sensory information through the peripheral nerves and the spinal cord is severely affected. There is also some impairment of muscle-controlling signals from the cerebellum and spinal cord. These problems lead to the progressive loss of balance, coordination and muscle strength that characterize FRDA. Further, patients often develop a hypertrophic cardiomyopathy that is likely the cause of premature death. Enlargement of the heart, irregular heartbeat and other symptoms of heart trouble are evident.
It is believed that the frataxin protein regulates the levels of iron inside the mitochondria which is necessary for using oxygen to produce energy. Frataxin appears to act as a storage depot for iron, releasing it only when it's needed for synthesis of enzymes in the mitochondrial. Therefore, a deficiency of frataxin results in a deficiency of these enzymes and further reduces mitochondrial function which likely explains why Friedreich ataxia affects cells of the nervous system and heart.
To date, no treatment exists for stopping or slowing down the negative effects of FRDA. Current therapeutic approaches in clinical use or under evaluation are directed at alleviating symptoms and maximizing quality of life. Physical therapy and speech therapy have been used to improve movement. Further, some medications have been used to treat heart disease. Thus, there is an important need for a novel therapeutic approach to treat the symptoms associated with FRDA.